A Study to Investigate the Safety and Immunogenicity of Monovalent Omicron LP.8.1-Adapted BNT162b2 COVID-19 Vaccine in Adults ≥ 65 Years of Age and High-Risk Adults 18–64 Years of Age (Preliminary Results)

Background/Objectives: This study evaluated the Omicron LP.8.1 variant-adapted BNT162b2 mRNA vaccine (LP.8.1-adapted BNT162b2). Methods: This analysis is part of an ongoing phase 3 open-label study evaluating the immunogenicity, safety, and tolerability of LP.8.1-adapted BNT162b2. Reported here are descriptive 2-week post-vaccination results in 18–64 -year-olds at high risk of severe COVID-19 and in ≥65-year-olds who received the Omicron KP.2-adapted COVID-19 vaccine ≥ 6 months previously. Primary immunogenicity endpoints included neutralizing antibody geometric mean titers (GMTs) against LP.8.1 and KP.2 at 2 weeks after vaccination and geometric mean fold rises from baseline to 2 weeks after vaccination. Results were compared with a historical control group of adults who received KP.2-adapted BNT162b2 in a previous study. Tolerability and safety were also assessed. Results: Overall, 104 participants received LP.8.1-adapted BNT162b2 (18–64-year-olds, n = 51; ≥65-year-olds, n = 53). Baseline neutralizing GMTs were higher in LP.8.1-adapted BNT162b2 recipients than in the historical control group of KP.2-adapted BNT162b2 recipients against both sublineages (248 vs. 157 against LP.8.1; 372 vs. 187 against KP.2). Serum-neutralizing LP.8.1 and KP.2 GMTs increased 2 weeks after vaccination with LP.8.1-adapted BNT162b2 (1752 against LP.8.1; 2104 against KP.2) and historical control groups (1555 and 2395, respectively), and across both age groups. Reactogenicity events with LP.8.1-adapted BNT162b2 were generally mild or moderate and occurred at generally similar frequencies in both age groups. Adverse events were reported in 4.8% of participants (all in 18–64-year-olds); no serious adverse events were reported. Conclusions: After 2 weeks of follow-up, and in a small sample size, LP.8.1-adapted BNT162b2 was immunogenic in ≥65-year-olds and ≥18-year-olds at high risk of severe COVID-19. The safety and tolerability profile for LP.8.1-adapted BNT162b2 was consistent with the current US prescribing information for BNT162b2 and that of other variant-adapted BNT162b2 vaccines (Clinicaltrials.gov Identifier: NCT07069309, registered 16 July 2025).